The objectives of this program project grant are to study the relations of hepatitis B virus (HBV) to: 1) primary hepatocellular carcinoma (PHC), and 2) cancer following tissue (particularly kidney) transplantation. The several stages of events which may lead to cancer will be studied by the testing of specific hypotheses generated from our previous work. These include for PHC: 1) maternal transmission of HBV, 2) differential dissemination of HBV among family members, 3) development and maintenance of the chronic HBV carrier state, 4) development of cirrhosis, 5) development of PHC. The eventual objective is the design of strategies for prevention of PHC. A related project is the continuation of our studies of blood polymorphisms which are either directly or indirectly related to the polymorphic nature of HBV antigens. For the second group of studies we will investigate: 1) the relation of HBV infection to the development of renal disease, 2) variation of responses to HBV infection in renal dialysis patients, 3) relation of HBV infection to transplant rejection, 4) the relation of the original renal disease, response to HBV infection, and transplantation outcome to development of cancer. Allied projects include studies of the pathogenesis of chronic lymphocytic leukemia and the T-cell form of acute lymphocytic leukemia. The methods to be used include: epidemiologic field work, clinical observations in our Clinical Research Unit, and laboratory immunology, biochemistry, and molecular biology.